When a person suffers a severe brain or spinal cord injury, the damage caused by the initial trauma is often just the beginning. Trauma can set off cascades of events that continue to damage the nervous system for days or months, causing additional neurological problems, paralysis, and even death.

In an article published in The Quarterly Review of Biology, researchers from Purdue University’s Center for Paralysis Research detail the disturbances from the systemic to the molecular that underlie this secondary injury in the nervous system, and suggest new approaches for combating it.

Stroke, traumatic brain injury, and spinal cord injury affect millions of people each year in the U.S. Despite their prevalence, treatment for these maladies has not improved much since World War II, say the article’s authors, Richard Ben Borgens and Peishan Liu-Snyder. Secondary injury, which often destroys nerves and even kills cells that were unharmed in the initial injury, is a big reason why these traumas are so hard to treat.

One important type of secondary injury begins when a blow to the head or stroke ruptures cell membranes, allowing the insides of cells to leak out and disrupting the physiology of the cells. This disruption produces free radicals that react with the fatty material in cell membranes, in turn producing extremely toxic byproducts called aldehydes. These aldehydes, some of which are chemically identical to known industrial pollutants, spread out from the wound site to destroy otherwise healthy cells

Researchers have tried unsuccessfully to prevent this “bystander damage” by targeting the damaging free radicals with mega-doses of antioxidant vitamins. Borgens and Liu-Snyder suggest that this approach has failed because free radicals are not the worst part of the cascade. Aldehydes are the real problem.

“There is no doubt that these aldehydes are critical—perhaps the most damaging endogenous factors in the secondary injury chemical cascades,” Borgens and Liu-Snyder write. “They are indeed guilty of cell murder and assault.”

Borgens and Liu-Snyder suggest not worrying so much the free radicals, and instead offer a “two-pronged approach to deal with secondary injury.”

First, they suggest attacking “the truly most ‘upstream’ biology—that of membrane disruption.” New polymers have been developed recently that can seek out damaged cell membranes and form a patch. These compounds, delivered via I.V. drip, could potentially head off the cellular leakage that starts the production of aldehydes.

Second, Borgens and Liu-Snyder suggest attacking the aldehydes themselves. “It is these endogenous toxins that must be controlled if the catastrophic damaging effect of progressive, self-sustaining, secondary injury is to be reduced or eliminated.” Two drugs, one a blood pressure drug and the other an antidepressant, have been shown to bind to aldehyde compounds, neutralizing them. Perhaps these drugs or ones like them could reduce bystander damage.

Research on these approaches is ongoing. Borgens and Liu-Snyder are optimistic that a deeper understanding of secondary injury—one that is just now coming into view—will help to guide successful new treatments.

The premier review journal in biology since 1926, The Quarterly Review of Biology publishes articles in all areas of biology but with a traditional emphasis on evolution, ecology, and organismal biology. QRB papers do not merely summarize a topic, but offer important new ideas, concepts, and syntheses. They often shape the course of future research within a field.